Particle separation is of great interest to many biological and biomedical applications. Hydrodynamic and bulk acoustic-based techniques have been used to focus sample core flows within sheath fluid. With respect to hydrodynamic focusing, conventional devices that have been employed to implement sheath flow have relatively complex designs and are relatively difficult to fabricate. Bulk acoustic wave (BAW) techniques, which may provide focusing of particles based on size and density in microfluidic chips, typically require that the microfluidic channels be formed of a material having excellent acoustic reflection properties (such as silicon and glass). Unfortunately, some less expensive, more commonly used, polymeric materials generally do not have such excellent acoustic reflection properties. Moreover, BAW transducers may be bulky.
More recently, surface acoustic wave (SA techniques have been developed to focus, manipulate and/or separate particles flowing within microfluidic channels. A SAW preferentially travels along the surface of a material rather than through the bulk of the material (generally, the amplitude of the acoustic wave decays exponentially transverse to the surface of the material). “Leakage” of SAWs into the fluid within the microfluidic channel results in pressure gradients in the fluid and/or streaming of the fluid. Acoustic particle manipulation may be applied to virtually any type of particle as it does not depend on the charge, polarity or labeling of the particles.
In general, surface acoustic waves propagate along a stress-free plane surface of an elastic solid substrate. Surface acoustic waves have an essentially exponential decay of amplitude into the substrate and therefore most of the displacement of the substrate occurs within about one wavelength of the surface.
A surface acoustic wave may be generated using an inter-digitated transducer (IDT) supported by a piezoelectric substrate. The transducer may be formed of two comb-shaped electrodes having interlocking teeth or fingers. An IDT converts periodically-varying electrical signals into mechanical vibrations or acoustic waves able to travel along the surface of a material. The frequency of the SAW generated by an IDT may be controlled by controlling the periodic spacing of the teeth or fingers of the IDT. As a non-limiting example, a piezoelectric substrate may be formed of a ferroelectric material such as lithium niobate.
SAW techniques may involve standing surface acoustic waves (SSAW) or travelling or streaming surface acoustic waves (TSAW). For example, a SSAW may be generated using a pair of IDTs that may be placed on the substrate on opposite sides of the microfluidic channel, with a particle focusing region being defined between the SSAW generators, The SSAW induces standing pressure waves, i.e., pressure forces or gradients associated with nodes or anti-nodes, within the fluid in the particle focusing region, and these gradients may be used to manipulate suspended particles.
U.S. Pat. No. 8,573,060 to Huang et al. discloses a microfluidic device wherein particles associated with a sample flowing within a channel are concentrated within a particle focus region of the channel by the effects of the SSAW. Referring to prior art FIG. 1 (taken from U.S. Pat. No. 8,573,060) a standing surface acoustic wave focusing device is schematically illustrated as a pair of IDTs deposited on a piezoelectric substrate and a microfluidic channel formed in a layer bonded to the substrate and positioned between the two IDTs. The pair of IDTs 18, 20 generates interfering surface acoustic waves, thereby creating a standing surface acoustic wave with pressure nodes (or anti-nodes) within the channel 10. Particles 12 suspended within a fluid medium 13 flowing within the channel 10 are focused to a narrow particle stream 14 at a pressure node located at the center of the channel as they flow through the particle focusing region. The lower portion of FIG. 1 schematically illustrates an enlarged cross section of the microfluidic channel to show how the standing surface acoustic wave pressure field inside the channel induces particles to collect at the pressure node. U.S. Pat. No. 8,573,060, issued Nov. 5, 2013 (U.S. Ser. No. 12/631,059) is incorporated by reference herein in its entirety.
US Patent Publication No. 2013/0213488 to Weitz et al. discloses a microfluidic device for sorting droplets or particles using TSAW. As with U.S. Pat. No. 8,573,060, US 2013/0213488 discloses that the surface acoustic waves may be created using a surface acoustic wave generator such as an IDT coupled to a material such as a piezoelectric substrate. However, in contrast to U.S. Pat. No. 8,573,060, US 2013/0213488 does not use the IDT to create interfering surface acoustic waves and a concomitant standing surface acoustic wave (SSAW), but rather to create traveling surface acoustic waves (TSAW). Referring to prior art FIG. 2 (taken from US 201310213488), the TSAW propagates on the surface of a piezoelectric substrate (1) and leaks into the fluid within the microfluidic channel (4) as a longitudinal wave. This leaked longitudinal wave causes acoustic streaming as a result of the compressibility of the bulk fluid. Particles located within the plug or droplet of acoustically streamed bulk fluid may be moved with the droplet. By controlling the applied voltage to the DT, streaming of the fluid within the microfluidic channel may be generated and used to individually direct or sort selected droplets within the microfluidic channel to particular channels or regions. As such, the traveling surface acoustic wave may act as a particle switch on a particle-by-particle basis. In FIG. 2, the SAW is shown additionally coupled to the microfluidic channel (4) via a water/glass coupling region. The SAW traveling along the piezoelectric substrate (1) is refracted as a longitudinal wave into a layer of water (2) and is subsequently refracted as a transverse wave into a layer of glass (3). At the top of the glass layer (3), the wave is refracted again, entering the water-filled channel (4) and causing acoustic streaming as indicated. US Patent Publication No. 2013/0213488 (U.S. Ser. No. 13/818,146, filed Aug. 23, 2011) is incorporated by reference herein in its entirety.
US Patent Publication No. 2014/0008307 to Guldiken et al. discloses a two-stage microfluidic device for focusing and separating particles flowing within a channel using standing surface acoustic waves. The two-stage microfluidic device has both a particle focusing stage and a particle separating stage, which is located downstream of the particle focusing stage. The particle focusing stage includes a pair of IDTs that generate a standing surface acoustic wave for focusing particles to a single pressure node (or anti-node) in the center of the channel, similar to the SSAW of U.S. Pat. No. 8,573,060. The particle separating stage includes a second pair of IDTs that also generates a standing surface acoustic wave. However, in this particle separating stage, the SSAW forms a periodic distribution of a plurality of pressure nodes and anti-nodes within the channel, thereby dividing the particles as they flow along a length of the channel into a plurality of particle streams aligned with the plurality of nodes or anti-nodes. The particles may be segregated based on their volume, density, compressibility or other acoustic contrast factor. Downstream of the particle separating stage, the various segregated streams of particles may flow into multiple collection outlets that are aligned with the streams. Guldiken also describes a method for fabricating and integrating the two-stage microfluidic device for focusing and separating particles flowing within a channel using IDTs to generate standing surface acoustic waves. US Patent Publication No. 2014/0008307 (U.S. Ser. No. 14/007,483, filed Mar. 30, 2012) is incorporated by reference herein in its entirety.
IDTs that are tunable have also been developed. US Patent Publication No. 2013/0192958 to Ding et al. discloses variable frequency or “chirp” IDTs having a gradient in their finger period, allowing them to resonate over a range of frequencies when the input frequency is varied. By varying the input frequency of a single pair of chirp IDTs, the pressure nodes may be generated at different locations across a microfluidic channel, such that depending upon the selected input frequency, particles flowing within the channel may be directed to a specific collection channel. In another embodiment, orthogonally positioned pairs of chirp IDTs may create SSAWs having pressure nodes (or anti-nodes), the location of which can be precisely adjusted by varying the input frequency to the IDTs. US Patent Publication No. 2013/0192958 (U.S. Ser. No. 13/755,865, filed Jan. 31, 2013) is incorporated by reference herein in its entirety.
US Patent Publication No. 2014/0033808 to Ding et al. discloses a pair of IDTs for creating a SSAW having a pressure node (or anti-node) that is obliquely aligned with the longitudinal axis of the flow channel. Thus, certain particles traveling down the channel will be repositioned within the channel due to the acoustic radiation forces created by the obliquely aligned pressure nodes (or anti-nodes). US Patent Publication No. 2014/0033808 (U.S. Ser. No. 13/995,709, filed Jul. 31, 2013) is incorporated by reference herein in its entirety.
PCT Publication WO 2014/004630 to Weitz et al. discloses using a pair of IDTs to create a “traveling” or “shifting” standing surface acoustic wave (TSSAW). U.S. Pat. No. 8,573,060, discussed above, employs a pair of IDTs, each generating a surface acoustic wave having the same frequency as the other, such that the interference of these surface acoustic waves creates stationary pressure nodes or antinodes. WO 2014/004630 discloses employing a pair of IDTs wherein each generates a surface acoustic wave having a frequency that slightly differs from the other. This slight mismatch in frequency creates standing waves having pressure nodes that slowly shift or move toward one of the pair of IDTs. PCT Publication WO 2014/004630 (Application No. PCT/US2013/047829 filed Jun. 26, 2013) is incorporated by reference herein in its entirety.
None of the above-cited documents disclose the use of SAW techniques for multiple channels provided on a single chip.